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The SAV001-H vaccine is considered as the first genetically modified version of the killed whole HIV-1 vaccine.

According to Dr. Kang, HIV-1 strain is genetically engineered such that first, “the gene responsible for pathogenicity, known as nef” is removed to make it non-pathogenic and then
the signal peptide gene is replaced with a honey bee toxin (melittin) signal peptide to make the virus production much higher and faster.[1]
In the signal peptide exchange process, another gene called vpu is lost due to an overlapping.[2]

Finally, this genetically modified version of HIV-1, (i.e., HIV-1 virus with nef negative, vpu negative and signal peptide gene replaced with honey bee’s)
grown in human T-lymphocytes (A3.01 cell line) are collected and purified before inactivating them by AT-2 (aldrithiol-2 or 2,2'-Dipyridyldisulfide) chemical treatment and gamma irradiation.
AT-2 chemical treatment is used because it does not affect the viral structure and immunogens.[3]

This killed virus vaccine approach has successfully prevented polio, influenza, cholera, mumps, rabies, typhoid fever and hepatitis A for decades.
At the moment, there are 16 animal vaccine based on this killed virus method including the feline immunodeficiency virus (which is closely related to HIV) vaccine for cats.

Funded by Sumagen Canada, the government of Canada and the Bill and Melinda Gates Foundation,[5] it started in March 2012 to assess its safety, tolerability, and immune responses.
This trial was a randomized, double blinded (both subject and investigator), placebo-controlled study,
following intramuscular administration to 33 chronic HIV-1 infected individuals under the treatment with HAART.

The study was completed in August 2013 and reported no serious adverse effects while boosting antibodies in the volunteers injected with SAV001-H vaccines.
According to the researchers, the antibody against gp120 surface antigen and P24 capsid antigen increased up to 6-fold and 64-fold, respectively, and the increased level of antibody was continued throughout the 52-week study period.[6]
Moreover, broadly neutralizing antibodies were found in some blood samples of the participants.

Phase II clinical trial

The Phase II clinical trial is expected to begin in 2018 [7] in the United States to measure immune responses.
The researchers plan to recruit about 600 HIV-negative volunteers who are in the high risk category for HIV infections such as commercial sex workers,
men who have sex with men (MSM), injecting drug users, and people who have unsafe sex with multiple partners.

Despite the fact that this killed whole virus strategy is widely exercised to prevent diseases like polio, influenza, cholera, mumps, rabies, typhoid fever and hepatitis A in the past,
it failed to receive any serious attention in the effort to develop vaccines against HIV for various scientific, economical and technical reasons.

First, there are risks associated with inadequately inactivated or not killed HIV remaining in vaccines. Second, a massive production of HIV is not economically feasible, if not impossible.
Third, many researchers tend to believe that when HIV is killed or inactivated by chemical treatment, it loses its antigenicity and thus fails to induce both neutralizing antibodies and
cytotoxic T-lymphocyte or CD8+ T cells (CTL). Fourth, the early studies with the monkeys using the killed simian immunodeficiency virus (SIV) vaccine showed some optimism but it turned out that
the protection was attributable to responses to both the cellular proteins on the SIV vaccine and on the challenge virus grown not in monkey cells but in human cells.
Fifth, the fact that “lab-adapted HIV-1 appeared to lose envelop glycoprotein, gp120, during preparation” was considered a crucial barrier to this method.[9] Nevertheless, to date many scientists and researchers insist on a belief that the killed whole virus strategy is a feasible option for an HIV vaccine.

Indeed, Jonas Salk developed a therapeutic HIV vaccine in 1987, called Remune now being developed by Immune Response BioPharma, Inc.,[10] is based on the killed whole virus approach. Remune vaccine has completed over 25 clinical studies to date and showed a robust mechanism of action restoring white blood cell counts in CD4 & CD8 T cells by reducing viral load and increasing immunity.

Also, a group of researchers and professionals in the field of HIV strongly advocates that the killed HIV approach must be taken to fight back the global HIV and AIDS epidemic.[11][12] The International AIDS Vaccine Research (IAVA) issued a report on “Whole Killed AIDS Vaccines” in 1999 reviewing a diverse aspect of the killed virus approach.[13]

The developer of SAV001-H, Dr. Chil-yong Kang, is a professor of Virology in the Department of Microbiology and Immunology, Schulich School of Medicine & Dentistry at the University of Western Ontario
since 1992. In addition to HIV preventive and therapeutic vaccine Dr. Kang is developing a second generation vaccine against hepatitis B and hepatitis C virus. To date, He has published 135 peer reviewed research papers in highly prestigious scientific journals, 149 scientific proceedings and abstracts in fields of virology and molecular biology.[14]

The study is sponsored by Sumagen, a subsidiary of Curocom (a KOSDAQ listed company in Korea, stock ticker no: 040350) and has been supported by the government of Canada as well as the Bill and Melinda Gates Foundation.
The patents related to the SAV001 vaccine were registered in more than 70 countries, including the U.S., the European Union, China, India, and South Korea.[15]